1984 Volume 9 Issue SupplementI Pages 89-108
The effect of azosemide (SK-110), and its metabolites, 5-(2'-amino-4'-chloro-5'-sulfamoylphenyl)-tetrazole (M-1), 2-thiophenecarboxylic acid (TC), on mouse liver was investigated using biochemical and pathological parameters as indices of hepatotoxicity. The effects were compared with that of furosemide (FM) administration. A single dose of each compound was administered orally, or intraperitoneally, while multiple oral dosing was carried out once daily for a week. The results are summarized as follows: 1) SK-110 did not produce hepatotoxicity even after a single p.o. dose as high as 5000 mg/kg, a single i.p. dose of 400 mg/kg, or multiple p.o. doses of 700mg/kg/day. 2) M-1 also did not produce hepatotoxicity even after a single p.o. dose of 4000 mg/kg or multiple p.o. doses of 550 mg/kg/day. TC did not exert hepatotoxicity after a single i.p. dose of 150 mg/kg or multiple p.o. doses of 250mg/kg/day, but did produce hepatotoxicity after a single p.o. dose of more than 1000 mg/kg. However, it was presumed that, in vivo, TC formed as a metabolite of administered SK-110 would hardly produce hepatotoxicity. 3) FM produced hepatotoxicity after a single p.o. dose of more than 800mg/kg, or a single i.p. dose of more than 200 mg/kg, but not after multiple p.o. doses of 700 mg/kg/day. Based on these findings, it was concluded that, in contrast to FM, SK-110 had no hepatotoxic effect on the mouse liver.
